Bone marrow transplantation (BMT) is the only curative treatment for a large number of hematological malignant disesase including leukemias, lymphomas and multiple myeloma. Transplantation of bone marrow from a healthy donor not only permits the use of intensive marrow ablative antileukemia treatment but also confers an immune response from the marrow graft against the leukemia. This graft versus leukemia (GVL) effect is very powerful and if harnessed could have great potential as a form of immunotherapy for leukemia. The current problem with mainpulating GVL is our frequent inability to separate this useful immune response from the harmful graft versus host disease (GVHD) effect also caused by donor immune cells after transplant. GVHD accounts for much of the mortality following BMT and limits the use of donor BMT to very well matched donors either selected from the family or from the panel of volunteers. If it became possible to carry out BMT which did not caue GVHD but conferred GVL the procedure could not only be applied safely to many more patients who at present are not considered for BMT because of age or because the best donor is not fully matched. The GVL effect would make transplantation from a healthy donor more effective than the alternative procedure of an auto-transplant (where the patient's own marrow is used for the transplant.) This program aims firstly to carry out clinical trials which focus on ways to prevent GVHD whils conserving GVL, secondly to understand the mechanisms involved in the immune attack against the host and the leukemia and thirdly to use this knowlege to use in clinical trials aimed at giving GVL reacting cells to prevent relapse of leukemia after marrow transplant.